PML diagnosis

Question

Dear Doctor,

Thank-you for being one of the many in providing a very informative web site for asking difficult questions. I have been diagnosed as HIV positive since early 1996 and been on antiviral treatments since. While having a long antiviral history I did have a period of non-compliance in 1999 which resulted in a hospitalization (5/99) and subsequent diagnosis of toxoplasmosis(1999).

I have recovered well in the period since 1999 2005. I have achieved an undetectable viral load and a CD4 abs 567 (03/05/05). I have been on a resume consisting of Abacavir (Ziagen) 600mg daily, Viread (Tenofovir) 300mg daily, Nevirapine 200mg x twice daily, Lamividome (3TC) 300mg daily. I also take 2mg daily of Clonazepam daily for seizures (suffered 2 seizures in the period 1999 2005).

My question is in regards with more recent developments. I noticed approximately 6 months ago my speech was becoming slurred, with laboured voice production and some problems with balance. I brought this to my GPs and HIV specialist who subsequently referred me to a Prof. (Neurologist). I had MIR scans done (Comparison MIRs unavailable) which brought into contention the possibility of PML (Progressive Multifocal encephalopathy).

The Prof, my GP and I discussed the findings of the MIR where the radiologist questioned the possibility of PML. My GP discounts PML due to the medication regime. The Prof. has requested a Lumber Puncher to determine if the JC virus is present. I have read that such testing of JC virus via this method - spinal fluid, blood test or urine testing will not be inconclusive as 80-85% of all adults are exposed to this virus worldwide. PMLs occurrence is primarily in those with advanced stages of disease with a very low CD4 count. I am aware it can occur in HIV infected people with CD4 counts above 500.

I am aware of the difficulty in the diagnosis of PML. A brain biopsy will produce a better, or rather, discount other viral infections.

What, if any, are more recent developments for a conclusive diagnosis of PML?

Given this information on the difficulty in diagnosis of PML (which may be as old as 1/2003) is there other means of indicting active PML?

Are there any alternative treatments apart from CMV drug (cidofovir), than the anti-viral medications I am currently on?

Answer

PML is difficult to diagnose. It is usually diagnosed based on clinical signs and imaging studies. Common signs are focal weakness, gait abnormalities or visual field cuts. MRI scan sometimes shows signs suggestive of PML. Routine CSF test are usually normal or show nonspecific changes. CSF PCR detection of JC virus DNA has been used in the diagnosis of PML, and is available in some commercial laboratories.

The main treatment approaches involve using the antiretroviral meds and sometimes the addition of cidofovir. This drug has significant side effects and is usually used only when the ART drugs by themselves don't prevent the progression of the neurologic symptoms.